Genetics of Primary Ciliary Dyskinesia

NCT02389049 | Completed DMC

• 2 other identifiers: 14-1225U54HL096458-11
• Study Type: observational
• Target: 320
• Locations: 2 countries
• Sites: 8

Brief Summary

This study is designed to study DNA sequencings for mutations in a research genetic test panel of genes (which contains all 32 known and/or published genes associated with PCD). The study aims to show that about 70% of PCD patients have biallelic mutations in one of these genes. This project will enroll patients who have already had a clinical evaluation, and have clinical features consistent with PCD.

Conditions

Primary Ciliary Dyskinesia; Kartagener Syndrome

Keywords

Primary Ciliary Dyskinesia; Kartagener Syndrome

Outcome Measures

Primary Outcomes (1)

• Confirm PCD diagnosis in patients using a panel of 32 genes

  The primary objective is to perform research genetic (Ampliseq panel) testing in patients who are known or suspected to have PCD, based on previous research or future clinical and lab characterization by certified clinical research sites. We will define the prevalence of biallelic PCD-causing mutations in patients who fulfill criteria of very high likelihood of PCD, as well as prevalence in other patients with some features of PCD. We anticipate successful completion of this objective will provide the foundation for development of clinically available genetic test panels, particularly as additional PCD genes are identified.

  Up to 5 years

Secondary Outcomes (1)

• Identify patients with PCD who do not have a biallelic PCD-causing mutation

  Up to 5 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study participants should have 2 or more clinical features of PCD.

You may qualify if:

• Any patient who has ≥ 2 clinical features (+/- lab) characteristic of PCD, including:
• Neonatal respiratory distress after term (or near-term) birth
• and/or laterality defect ( situs inversus or heterotaxy)
• and/or daily wet cough before 6 months of age
• and/or middle ear disease
• and/or chronic nasal congestion before 6 months of age
• and/or bronchiectasis
• and/or male infertility due to sperm tail dysfunction
• and/or low nasal nitric oxide levels (\<77 nanoliters/minute)
• and/or defective ciliary ultrastructure

You may not qualify if:

• Known diagnosis of cystic fibrosis with classic clinical presentation and elevated sweat chloride levels and/or two known disease-causing Cystic Fibrosis transmembrane conductance regulator (CFTR) mutations, or documented primary or acquired immunodeficiency.
• Known explanation for bronchiectasis (and other clinical features), such as α1-antitrypsin deficiency (ZZ or ZS), inflammatory bowel disease or rheumatoid arthritis.
• Any patient who is unwilling or unable to provide consent or to comply with the testing required in this protocol
• A participant should not be in the study if they have not had a standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Rare Diseases Clinical Research Network: collaborator
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (8)

Stanford University

Palo Alto, California, 94304, United States

Location

The Children's Hospital, Denver

Aurora, Colorado, 80045, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63110, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Children's Hospital and Regional Medical Center, Seattle

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

McGill University

Montreal, Quebec, Canada

Location

Related Publications (1)

• Kaspy KR, Dell SD, Davis SD, Ferkol TW, Rosenfeld M, Sagel SD, Milla C, Olivier KN, Barber AT, Wee W, Lin FC, Li L, Rampakakis E, Zariwala MA, Knowles MR, Leigh MW, Shapiro AJ. Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia. Chest. 2024 May;165(5):1070-1081. doi: 10.1016/j.chest.2023.12.005. Epub 2023 Dec 9.

  PMID: 38072392 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood or buccal samples

MeSH Terms

Conditions

Ciliary Motility Disorders; Kartagener Syndrome

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Bronchiectasis; Bronchial Diseases; Respiratory System Abnormalities; Dextrocardia; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Situs Inversus

Study Officials

• Michael Knowles, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2015
• First Posted: March 17, 2015
• Study Start: February 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 10, 2022

Record last verified: 2022-08

Locations

US (6); CA (2)